Dataset Information

Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants.

ABSTRACT:

Background

The fraction of exhaled nitric oxide (Feno) value is a biomarker of eosinophilic airway inflammation and is associated with childhood asthma. Identification of common genetic variants associated with childhood Feno values might help to define biological mechanisms related to specific asthma phenotypes.

Objective

We sought to identify the genetic variants associated with childhood Feno values and their relation with asthma.

Methods

Feno values were measured in children age 5 to 15 years. In 14 genome-wide association studies (N = 8,858), we examined the associations of approximately 2.5 million single nucleotide polymorphisms (SNPs) with Feno values. Subsequently, we assessed whether significant SNPs were expression quantitative trait loci in genome-wide expression data sets of lymphoblastoid cell lines (n = 1,830) and were related to asthma in a previously published genome-wide association data set (cases, n = 10,365; control subjects: n = 16,110).

Results

We identified 3 SNPs associated with Feno values: rs3751972 in LYR motif containing 9 (LYRM9; P = 1.97 × 10(-10)) and rs944722 in inducible nitric oxide synthase 2 (NOS2; P = 1.28 × 10(-9)), both of which are located at 17q11.2-q12, and rs8069176 near gasdermin B (GSDMB; P = 1.88 × 10(-8)) at 17q12-q21. We found a cis expression quantitative trait locus for the transcript soluble galactoside-binding lectin 9 (LGALS9) that is in linkage disequilibrium with rs944722. rs8069176 was associated with GSDMB and ORM1-like 3 (ORMDL3) expression. rs8069176 at 17q12-q21, but not rs3751972 and rs944722 at 17q11.2-q12, were associated with physician-diagnosed asthma.

Conclusion

This study identified 3 variants associated with Feno values, explaining 0.95% of the variance. Identification of functional SNPs and haplotypes in these regions might provide novel insight into the regulation of Feno values. This study highlights that both shared and distinct genetic factors affect Feno values and childhood asthma.

SUBMITTER: van der Valk RJ

PROVIDER: S-EPMC4334587 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Publications

Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants.

van der Valk Ralf Jp RJ Duijts Liesbeth L Timpson Nicolas J NJ Salam Muhammad T MT Standl Marie M Curtin John A JA Genuneit Jon J Kerhof Marjan M Kreiner-Møller Eskil E Cáceres Alejandro A Gref Anna A Liang Liming L LL Taal H Rob HR Bouzigon Emmanuelle E Demenais Florence F Nadif Rachel R Ober Carole C Thompson Emma E EE Estrada Karol K Hofman Albert A Uitterlinden André G AG van Duijn Cornélia C Rivadeneira Fernando F Li Xia X Eckel Sandrah P SP Berhane Kiros K Gauderman W James WJ Granell Raquel R Evans David M DM St Pourcain Beate B McArdle Wendy W Kemp John P JP Smith George Davey GD Tiesler Carla Mt CM Flexeder Claudia C Simpson Angela A Murray Clare S CS Fuchs Oliver O Postma Dirkje S DS Bønnelykke Klaus K Torrent Maties M Andersson Martin M Sleiman Patrick P Hakonarson Hakon H Cookson William O WO Moffatt Miriam F MF Paternoster Lavinia L Melén Erik E Sunyer Jordi J Bisgaard Hans H Koppelman Gerard H GH Ege Markus M Custovic Adnan A Heinrich Joachim J Gilliland Frank D FD Henderson Alexander J AJ Jaddoe Vincent Wv VW de Jongste Johan C JC

The Journal of allergy and clinical immunology 20131206 1

<h4>Background</h4>The fraction of exhaled nitric oxide (Feno) value is a biomarker of eosinophilic airway inflammation and is associated with childhood asthma. Identification of common genetic variants associated with childhood Feno values might help to define biological mechanisms related to specific asthma phenotypes.<h4>Objective</h4>We sought to identify the genetic variants associated with childhood Feno values and their relation with asthma.<h4>Methods</h4>Feno values were measured in chi ...[more]

PMID: 24315451

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Project description:ObjectiveAirway inflammation plays an important role in obstructive sleep apnea (OSA); exhaled nitric oxide is regarded as a noninvasive marker of airway inflammation. The aim of this study was to evaluate fractional exhaled nitric oxide (FeNO) and nasal nitric oxide (nNO) in patients with OSA.MethodsSeventy-five patients with OSA and 30 health controls were enrolled in this study. FeNO and nNO were measured before and after sleep. Nasal lavage was performed in 31 non-smoking individuals immediately after NO measurement in the morning. The sample of nasal lavage was taken for cell classification and analyzing interleukin 6 (IL-6) and interleukin 8 (IL-8).ResultsBoth FeNO and nNO were significantly higher in OSA (before sleep FeNO 21.08 ± 8.79 ppb vs.16.90 ± 6.86 ppb, p = 0.022; after sleep FeNO 25.57 ± 15.58 ppb vs.18.07 ± 6.25 ppb, p = 0.003; before sleep nNO 487.03 ± 115.83 ppb vs. 413.37 ± 73.10 ppb, p = 0.001; after sleep nNO 550.07 ± 130.24 ppb vs. 460.43 ± 109.77 ppb, p < 0.001). Furthermore, in non-smoking OSA, nNO levels were positively correlated with apnea hypopnea index (AHI) and average decrease of pulse arterial oxygen saturation (SpO2); after sleep, nNO was also positively associated to recording time with SpO2 < 90% and negatively associated to minimum SpO2. Both before and after sleep nNO levels were positively correlated with the percentage of neutrophils in nasal lavage (r = 0.528, p = 0.014; r = 0.702, p < 0.001, respectively). Additionally, before sleep nNO was also positively associated with IL-6 (r = 0.586, p = 0.005) and IL-8 (r = 0.520, p = 0.016) concentration.ConclusionThis study sustains the presence of airway inflammation in OSA patients with the increase of FeNO and nNO. The data suggests nNO might have greater value than FeNO since it positively correlated with OSA severity, and nNO is a potential bio-marker of nasal inflammation in non-smoking OSA patients.

Dataset Information

Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants.

Background

Objective

Methods

Results

Conclusion

Publications

Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants.

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